The usual aim in developing a chemical sensor or biosensor is to produce an electronic signal, which is proportional to the concentration of a specific chemical or set of chemicals (analyte), and with high specificity to the desired analyte. The sensor usually comprises two main components, a chemical or biological part that reacts or complexes with the analyte in question (ideally specifically) to form new chemical or biological products or changes in energy that can be detected by means of the second component, a transducer. The chemical/biological component can be said to act as a receptor/indicator for the analyte. A variety of transduction methods can be used including electrochemical (such as potentiometric, amperometric, conductimetric, impedimetric), optical, calorimetric and acoustic. After transduction the signal is usually converted to an electronic digital signal.
Since the signal generated by the chemical/biological reaction with the analyte is usually dependent not only on the concentration of the analyte but also on the characteristics of the sensor itself, such sensors usually require calibration before they can be utilized quantitatively. The way in which the signal varies with the analyte concentration determines the shape of the calibration curve (signal versus analyte concentration) and may define the number of calibration points. Typical calibration curves can be straight line, exponential, s-shaped etc and the principal of calibration applies to all methodologies of transduction for chemical or biological sensors.
Calibration of sensors with an invasive medical application has its own set of specific issues. Invasive or implantable medical sensors must be presented to the patient in a sterile condition, and are often single use, disposable devices. Ideally, the sensor should be calibrated just before its use because some sensor characteristics that can affect the calibration curve vary with time (ageing effect).
Sterilization of such devices can also provide difficulties. The sterilization process is typically carried out at the point of manufacture to avoid difficulties with poor or incomplete sterilization procedures at a hospital or clinic, and to save time on behalf of the clinician or nurse. Three forms of sterilization are commonly used for the sterilization of medical devices: steam, ethylene oxide, and irradiation.
Steam is usually used for metal surgical instruments, bandages and liquids within containers but is not appropriate for devices with low melting point plastic components or labile chemical or biological components since steam sterilization usually takes place at temperatures above 116 C.
Ethylene oxide sterilization is a surface sterilant that generally does not degrade the receptor and other materials that comprise a sensor, but should only be used to sterilize materials that are free from significant amounts of water, since the ethylene oxide can react with the water to form ethylene glycol. Thus ethylene oxide is the preferred means of sterilizing chemical sensors.
Ethylene oxide sterilization, however, has a number of drawbacks. Firstly, it is usual in sensor construction to immobilize the receptor to the transducer and this is usually achieved by the utilization of polymeric materials. If the sensor is to measure water-soluble analytes, and analytes soluble in blood plasma, the polymeric immobilization material must be hydrophilic (readily adsorb water) to allow the diffusion of the analyte through the immobilization material to the receptor material and allow measurement to take place. To sterilize such a sensor with ethylene oxide, all water must be removed from the hydrophilic material prior to sterilization.
Secondly, to calibrate a sensor that is to measure a water-soluble analyte at the point of use, the user must immerse the sensor in water based solutions of the analyte (or analogues of the analyte) whilst maintaining sterile integrity. However, a calibration vessel, containing calibration solution(s), cannot be sterilized with ethylene oxide, which is a surface sterilant, and therefore must be sterilized by a different process.
Irradiation, usually gamma irradiation, is a penetrating means of sterilization and can therefore sterilize liquids in containers. However, gamma radiation has been found to have an effect on calibration liquids that can adversely affect the operation of analyte sensors.
There is therefore a need for a calibrator, a sensor kit, and a sterilization method that avoids some or any of the above problems.